Since Moraxella catarrhalis is a common cause of otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD), there is considerable interest in developing vaccines to prevent these infections. In order to have a rational approach to developing a vaccine to prevent infections due to M. catarrhalis, it is important to know what constitutes a protective immune response. The approach to elucidating a protective immune response to infection caused by M. catarrhalis will involve studies with epidemiologically well defined clinical samples from a prospective study of COPD. The prospective study design and the well characterized samples provide the opportunity to identify immune responses which mediate protection from infection and/or clearance of M. catarrhalis from the human respiratory tract. The systemic and mucosal immune response will be studied in samples from patients who have cleared M. catarrhalis from their respiratory tracts and from adults who have experienced recurrent infections due to M. catarrhalis. Correlating the results of immunoassays with the subsequent clinical and microbiological outcome will allow predictions regarding immune responses which mediated clearance of colonization. Samples will be subjected to a series of several immunoassays to elucidate the nature of protective immune responses in humans. Such information is critical in developing a rational strategy for testing potential vaccine antigens for M. catarrhalis.